| First Author | Tiruppathi C | Year | 2020 |
| Journal | Mol Biol Cell | Volume | 31 |
| Issue | 11 | Pages | 1167-1182 |
| PubMed ID | 32238105 | Mgi Jnum | J:328464 |
| Mgi Id | MGI:6717864 | Doi | 10.1091/mbc.E19-12-0713 |
| Citation | Tiruppathi C, et al. (2020) EphB1 interaction with caveolin-1 in endothelial cells modulates caveolae biogenesis. Mol Biol Cell 31(11):1167-1182 |
| abstractText | Caveolae, the cave-like structures abundant in endothelial cells (ECs), are important for multiple signaling processes such as production of nitric oxide and caveolae-mediated intracellular trafficking. Using superresolution microscopy, fluorescence resonance energy transfer, and biochemical analysis, we observed that the EphB1 receptor tyrosine kinase constitutively interacts with caveolin-1 (Cav-1), the key structural protein of caveolae. Activation of EphB1 with its ligand Ephrin B1 induced EphB1 phosphorylation and the uncoupling EphB1 from Cav-1 and thereby promoted phosphorylation of Cav-1 by Src. Deletion of Cav-1 scaffold domain binding (CSD) motif in EphB1 prevented EphB1 binding to Cav-1 as well as Src-dependent Cav-1 phosphorylation, indicating the importance of CSD in the interaction. We also observed that Cav-1 protein expression and caveolae numbers were markedly reduced in ECs from EphB1-deficient (EphB1(-/-)) mice. The loss of EphB1 binding to Cav-1 promoted Cav-1 ubiquitination and degradation, and hence the loss of Cav-1 was responsible for reducing the caveolae numbers. These studies identify the crucial role of EphB1/Cav-1 interaction in the biogenesis of caveolae and in coordinating the signaling function of Cav-1 in ECs. |
